The aim of this program is to determine how growth factors and the signal transduction apparatus regulate early steps in the development of animal form. Three scientific projects track the signal transduction process program project. Dr. Stiles will extend work he initiated on the PDGF alpha receptor and its role in formation of embryonic mesoderm and neural crest. His work will focus on the mouse mutant "Patch" which carries a deletion of the PDGF alpha receptor subunit. Stiles will critically assess the role of PDGF alpha receptor activation in the patch mouse syndrome. Activation state- specific antibodies ill be used to display receptor activation. Dominant strains. Dr. Roberts will further detail the interplay between p21 ras and the serine/threonine kinases, Raf-1 and Map kinase which he and his colleagues discovered under auspices of this grant. In collaboration with Dr. Whitman he will search for new substrates for both Raf-1 and the map kinase (MEK) in mammalian cells Work will also proceed to extend our knowledge of the kinase signalling cascades to transcription factors in the nucleus. A key element of his project, construction of transgenic mouse strains expressing loss-of-function or gain-of-function mutations of Raf-1 will be done3 in collaboration with Dr. Stiles. Dr. Whitman is interested in the transduction of axial patterning signals in Xenopus. He will explore the role of Raf-1 in the establishment of the competence of early embryonic cells to respond to mesoderm inducers. He will also examine the role of the serine/threonine kinase GSK3 in mediating the action of signals responsible for establishment of the embryonic dorsal-ventral axis. Dr. Whitman will also collaborate with Dr. Roberts to search for Raf-1 substrates in the Xenopus system. The program faculty have a long and tangible history of productive interactions. They share ideas, biological reagents, common space and heavy instruments. They are further unified by core facilities for molecular biology, cell imaging and transgenic mouse research.